NeuroQuantology | December 2018 | Volume 16 | Issue 12 | Page 20-24 | doi: 10.14704/nq.2018.16.12.

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Gong Y., Clinical Evaluation of Event-Related Potential Functional Abnormalities in the ICA-based Primary Dysmenorrhea Mechanism 

Clinical Evaluation of Event-Related Potential

Functional Abnormalities in the ICA-based Primary
Dysmenorrhea Mechanism
Ying Cui1, Wenting Wang2, Xiuyan Yin3, Shanshan Tong4, Yufeng Gong5*

ABSTRACT
To analyze and study the clinical situation of abnormal event-related potential (ERP) functions in the mechanism
of ICA-based primary dysmenorrhea, this paper included 42 subjects with primary menstrual pain and 30 subjects
without the pain. Firstly, the two groups of subjects were compared in their low-frequency amplitudes during the
0.01-0.08 Hz frequency band. Then the variance analysis method was used to analyze whether there was band effect
in the low-frequency amplitude inter-group differences. Finally, the brain function network was isolated using the
independent component analysis method, and brain-wide differences between two groups were compared. Results
have shown significant differences in age and anxiety index between the two groups. Patients with primary menstrual
pain sees significant increase in the ALFF of the bilateral orbital frontal lobe and left middle cingulum, but dramatic
decrease in the ALFF of right angular gyrus and left parahippocampal gyrus, right middle temporal gyrus, and bilateral
inferior temporal gyrus, which provides a basis for abnormal low-frequency spontaneous brain activity in patients
with primary menstrual pain.
Key Words: ICA, Primary Dysmenorrhea Mechanism, ERP Abnormalities 20
DOI Number: 10.14704/nq.2018.16.12.1744 NeuroQuantology 2018; 16(12):20-24

Introduction displays no obvious genital organ disease in the

Primary dysmenorrhea is a gynecologic disorder that
causes spasmodic pain during the menstrual cycle and
increases the sensitivity of pain. It is characterized by
a period of one to three days during menstruation.
Generally speaking, adolescent female account
for a large proportion of patients with primary
dysmenorrhea. Dysmenorrhea refers to spasmodic
pains in the lower abdomen and at the waist before
and during menstruation, sometimes accompanied
by severe nausea, vomiting, and cold extremities,
which is more common in unmarried young
women. Clinically, dysmenorrhea is divided into two
major categories. One is primary dysmenorrhea,
also known as functional menstrual pain, which
pelvic gynecological examination and often occurs
shortly after the menarche. The other is secondary
dysmenorrhea, which is caused by identified disease,
such as genital inflammation, uterine fibroids,
endometriosis, and other genital diseases.
There are various reports on the incidence of
menstrual pain at home and abroad. According to a
sample survey conducted by the National Women’s
Menstrual Physiological Constant Working Group
in 2000, the incidence of primary menstrual pain in
China was 56.06%, 13.55% of which could hardly
work. In foreign countries, a Mexican survey showed
that the incidence of primary menstrual pain was
64.0%, with the mild pain of 36.1%, moderate pain

Corresponding author: Yufeng Gong

Address: 1Department of Obstetrics and Gynecology, Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang 157011, China;
2
Department of Physiology, Basic Medical College of Mudanjiang Medical University; Mudanjiang 157011, China; 3Department of Gynecology,
Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang 157011, China; 4Mudanjiang Medical University, Mudanjiang 157011, China;
5
*Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang 157009, China.
e-mail  gong_yufengok@163.com
Relevant conflicts of interest/financial disclosures: The authors declare that the research was conducted in the absence of any commercial or
financial relationships that could be construed as a potential conflict of interest.
Received: 18 June 2018; Accepted: 19 July 2018

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NeuroQuantology | December 2018 | Volume 16 | Issue 12 | Page 20-24 | doi: 10.14704/nq.2018.16.12.1744
Gong Y., Clinical Evaluation of Event-Related Potential Functional Abnormalities in the ICA-based Primary Dysmenorrhea Mechanism
of 43.8%, and severe pain of 20.1%, and 65% of them
was limited in actions due to menstrual pain (Ortiz et
al., 2010). A survey in the United States showed that
the incidence of primary menstrual pain was 88.0%
(Polat et al., 2009). From the previous surveys, we
found that the absenteeism rate of female workers
due to menstrual pain is approximately 34% to 50%,
and that about 10% of them would be unable to
work within 1 to 3 days per month. This can cause
economic losses of about 2 billion U.S. dollars per year
(Harel et al., 2006). In addition, patients with severe
menstrual cramps, if they still work, may not only
show lower capability but also cause accidents. The
difference in reported incidence between domestic
and foreign countries is huge, about 30% to 90%,
which may be due to the different health conditions,
cultural backgrounds, living conditions, and
diagnostic criteria in different countries (Patel et al.,
2006). The primary menstrual pain, with a relatively
high incidence, is a common health problem in all
countries of the world that seriously affects women’s
normal work and life.
Primary menstrual pain usually occurs several
months after the menarche. It mainly starts before
or at the onset of the menstruation, and reaches a
peak after 24 hours, featuring squeezing or cramping
pains, sometimes persistent blunt pain, or extending
to the lower back, leg or back pain, and often calms
down after 48 hours of menstruation. Sometimes
intimal casts or blood clots are excluded from the
vagina. Most patients are accompanied by nausea,
headache, constipation or diarrhea, and frequent
urination (Tu et al., 2009). Generally, after marriage
or childbirth, as female grows older, the pain will
disappear automatically, but a small number of
patients may still suffer after their 30s.
Increased endometrial prostaglandin and
secretion during menopause that lead to excessive
uterine contractions is currently considered to be the
main cause of menstrual pain. And some additional
causes include intrauterine ischemia and hypoxia
induced by excessive contractions, and the pelvic
pain fibers’ anaphylaxis of prostaglandins and
intracerebral peroxides. Of course, psychological
factor is also an important but not the main reason
for the pain.
Primary menstrual pain is mainly related to
uterine factors, endocrine factors, pain sensitization,
neurological and neurotransmitter factors, and
mental factors (Tu et al., 2010). Independent
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component analysis is a data-driven blind source
separation method that has been widely used in
the separation of brain function networks. In this
paper, 10 brain function networks were successfully
separated through the independent component
analysis method, and the network differences
between the two groups were compared one by one.
It was found that the network differences are mainly
concentrated in four networks: the default network,
the balance network, the sensory motor network,
and the basal ganglia network. All of these studies
have shown abnormal brain function in patients with
primary menstrual pain.
Experiments
General information
(1) The menstrual period is between 27 and 32
days; (2) The period of illness is more than 6
months; (3) The first onset should be within two
years of menarche; (4) During the last 6 months of
menstruation, the cramp index should be greater
than 4 (0 means no pain at all, while 10 means the
most painful). According to the criteria, 42 patients
with primary menstrual pain were recruited, and the
behavior index of each subject was tested, including
menstrual cycle, body mass index, anxiety index, 21
depression index, duration of onset, and pain index.
Experimental methods
All image data was obtained with Siemens 3T
MRI equipment at Affiliated Hongqi Hospital of
Mudanjiang Medical University. To reduce head
movements, the foam pad was used for fixation. For
each subject, the functional image was then scanned
with a gradient echo planar imaging sequence for 6
minutes. During the entire data scanning process,
subjects were required to close their eyes, try not to
think, and stay awake.
Data processing methods
In the Matlab R2010b, the resting state functional
magnetic resonance processing assistant software
DPARSFA2.2 was used, which is a data processing
toolkit that integrates the preprocessing module of
SPM8 with the post processing module of Rest.
A two-sample t test was performed on the
ALFF plots of the primary menstrual cramp group
and the healthy control group using Rest software,
with the age as a covariate, Bonferroni correction for
multiple comparison corrections, and p<0.005. The
results were superimposed on the template, leading
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NeuroQuantology | December 2018 | Volume 16 | Issue 12 | Page 20-24 | doi: 10.14704/nq.2018.16.12.1744
Gong Y., Clinical Evaluation of Event-Related Potential Functional Abnormalities in the ICA-based Primary Dysmenorrhea Mechanism 

to that there is a significant difference in the brain
regions between the menstrual pain group and the
control group.
Results and discussion
Analysis of clinical results
The clinical and demographic statistics are shown
in Table 1. Thirty healthy subjects and forty-two
subjects with the primary menstrual pain were
selected for the test. The results showed a significant
difference in age and anxiety index between the two
groups (p<0.001), but no significant difference in the
body mass index and depression index. The subjects
with primary menstrual pain has suffered the pain for
76.6 months (standard deviation: 28.4 months), with
the pain index of 7.9 (standard deviation: 5.66). All inter-
group tests were two-tailed and two-sample t tests.
One-sample t test results
The brain regions with significantly increased ALFF
values in both normal subjects and subjects with
primary menstrual pain were medial prefrontal,
precuneus, gyrus temporalis medius, and right
insula (p<0.001), while the brain regions with
both significantly decreased ALFF values were
parahippocampal gyrus, putamen, and middle
cingulum (p<0.001). For specific information, please
see Fig. 1 and 2.

22

Figure 1. Results of a single-sample t-test of a normal test

Figure 2. Results of single sample t test in patients with primary menstrual pain

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NeuroQuantology | December 2018 | Volume 16 | Issue 12 | Page 20-24 | doi: 10.14704/nq.2018.16.12.1744
Gong Y., Clinical Evaluation of Event-Related Potential Functional Abnormalities in the ICA-based Primary Dysmenorrhea Mechanism 

After ALFF of all subjects were obtained, the
two-tailed two-sample t test was adopted to identify
whether there was a significant difference between
the two groups (p<0.001). The results showed that
patients with primary menstrual pain, compared
with healthy subjects, sees significant
Two-sample t test results
Increase in the ALFF of the bilateral orbital frontal
lobe and left middle cingulum (p<0.001) (Fig. 3
and Table 2), and dramatic decrease in the ALFF of
right angular gyrus and left parahippocampal gyrus,
right middle temporal gyrus, and bilateral inferior
temporal gyrus (p<0.001).
Conclusion and outlook
In this paper, the resting-state fMRI technology was
adopted to study the ALFF of patients with primary
menstrual pain. The results showed that patients
with primary menstrual pain, compared with healthy
subjects, sees significant increase in the ALFF of the
bilateral orbital frontal lobe and left middle cingulum,
but dramatic decrease in the ALFF of right angular
gyrus and left parahippocampal gyrus, right middle
temporal gyrus, and bilateral inferior temporal gyrus.

23

Figure 3. Results of double sample t test for patients with primary menstrual pain and normal subjects

Table 1. Clinical Analysis

Mean ± standard deviation P
Project
Primary menstrual pain Health test
Number of participants 42 30
Age (years) 21.5±1.41 22.4±1.77 0.002*
Body mass index 20.2±1.84 19.7±1.66 0.242
Menstrual cycle 28.6±1.84 28.53±2.01 0.89
anxiety 28.60±5.21 25.23±6.25 0.027*
Depression 28.77±8.08 25.83±5.38 0.103
Course of disease (month) 76.66±28.41
Pain index 7.9±5.66
Note: * indicates a significant difference

Table 2. Significant activation areas and peak coordinates of patients with primary menstrual pain compared to normal subjects
Peak point coordinates (MNI)
Brain area hemisphere Voxel number T
X Y Z
Orbital frontal lobe R 6 24 63 -3 3.05
Orbital frontal lobe L 7 -36 54 -15 4.03
Cingulate belt L 8 -6 -42 48 3.74

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NeuroQuantology | December 2018 | Volume 16 | Issue 12 | Page 20-24 | doi: 10.14704/nq.2018.16.12.1744
Gong Y., Clinical Evaluation of Event-Related Potential Functional Abnormalities in the ICA-based Primary Dysmenorrhea Mechanism
Table 3. The areas with significant negative activation and peak coordinates of patients with primary menstrual pain are compared with healthy
subjects
Brain area hemisphere Voxel number
The angular gyrus R 11
Parahippocampal L 6
Middle temporal gyrus R 31
Inferior temporal gyrus L 16
Inferior temporal gyrus R 12
The orbital frontal lobe plays an important
role in sensory separation and avoidance behaviors,
because it is mainly involved in sensory integration,
monitoring the internal organ response and internal
state of the body, as well as assessing sensory responses
and regulation of autonomy. In addition, the orbital
frontal lobe is also involved in the pain and regulation
of pain. Studies have found that the orbital frontal
lobe can release endogenous opioids, an analgesic
substance. In view of the metabolic enhancement
of the thalamic-frontotemporal-forehead network,
it is predicted that the enhancement of the ALFF in
the orbital frontal lobe region may be attributed to a
chronic and abnormal sensation in the pelvic region,
which in turn has a negative effect on analgesia.
Many studies have shown that parahippocampal
gyrus is not only involved in the treatment of pain and
visceral sensation, but also enhances the memory of
information such as visceral pain and unpleasant
visceral sensation. Consistent with these studies, the
research has indicated that the parahippocampal
gyrus is negatively activated in patients with primary
menstrual pain, suggesting a decrease in pain-
regulatory capacity in menstrual pain patients and
a possible relief of the memory of this unpleasant
experience (Tu et al., 2013).
Studies have shown that the middle temporal
gyrus pathologically results in Alzheimer’s disease,
which is related to memory coding and self-cognition.
The functional abnormalities of the brain area in
the middle temporal gyrus indicate that primary
menstrual pain can affect the patient’s memory and
self-related functions (Vincent et al., 2011). In this
paper, the resting-state fMRI technology was adopted
to study the ALFF of patients with primary menstrual
pain. By comparing the ALFF of the two groups in the
resting state, it was found that patients with primary
menstrual pain, compared with healthy subjects, sees
significant increase in the ALFF of the bilateral orbital
frontal lobe and left middle cingulum, but dramatic
decrease in the ALFF of right angular gyrus and
left parahippocampal gyrus, right middle temporal
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Peak point coordinates (MNI)
T
X Y Z
48 -57 33 -3.85
-27 -33 -12 -3.62
54 -42 -15 -3.96
-54 -42 -18 -3.88
56 -40 -14 -3.58
gyrus, and bilateral inferior temporal gyrus. These
results provide a basis for abnormal low-frequency
spontaneous brain activity in patients with primary
menstrual pain. ALFF refers to the total energy in the
low frequency band, which is easily affected by some
physiological factors such as heartbeat, breathing,
etc., while the fALFF can better identify the low-
frequency ERP activity. This is the limitation of this
article. Therefore, in the future, the fALFF difference
should be further studied.
The pathogenesis of primary menstrual pain
is still not very clear at present, but it is generally
considered to be mainly related to uterine, endocrine,
nerve and neurotransmitter, and mentality. In this
paper, the f MRI imaging and some data processing
methods was used, in the hope of providing additional
help for the research on menstrual pain. 24
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